The deleterious effects of maternal smoking during pregnancy are well established. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated, is the recent, strong evidence, that smoking during pregnancy directly and adversely affects lung development. Respiratory problems associated with in utero tobacco exposure include decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS). Given the unfortunate prevalence of smoking during pregnancy and the resulting serious consequences, it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. We have begun to investigate this by administration of nicotine to timed-pregnant rhesus monkeys. In preliminary studies we have demonstrated that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal a irway dev elopment and that related effects can be reproduced in fetal monkey lung organ culture. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. Preliminary data further suggests that some of the effects of nicotine, acting though nicotinic receptors, may be mediated by antagonism of the mitogenic effects of peptide growth factors such as GRP. From these studies will come the first description of the effects of chronic nicotine exposure on lung function, a determination of the extent to which these effects are reversible, and a beginning understanding of the mechanisms underlying these effects. FUNDING Center-supported project PUBLICATIONS Sekhon HS, Jia Y, Kuryatov A, Cole L, Raab R, Whitsett JA, Lindstrom J, Spindel ER. Interaction of nicotine with nicotinic cholinergic receptors in fetal rhesus monkey lung. Soc Neurosci Abstr 24:335, 1998. Sekhon HS, Jia Y, Kuryatov A, Cole L, Raab R, Lindstrom J, Spindel ER. Interaction between gastrin-releasing peptide (GRP) and nicotine in primate lung development. In National Heart Lung and Blood Institute workshop on Molecular Embryology of the Lung (held in Bethesda, MD, June 1, 1998) (abstract).